scholarly journals Reverse complementary matches simultaneously promote both back-splicing and exon-skipping

2021 ◽  
Author(s):  
Dong Cao
Keyword(s):  
Larval Stage ◽  
Large Scale ◽  
Exon Skipping ◽  
The Other ◽  
Circular Rnas ◽  
Branch Points ◽  
Rna Seq ◽  
C Elegans ◽  
Neuronal Genes ◽  
Whole Transcriptome

Circular RNAs (circRNAs) play diverse roles in different biological and physiological environments. Understanding circRNA expression profile and how circRNAs are regulated help make better use of them. Here, using large-scale neuron isolation from the first larval stage (L1) of Caenorhabditis elegans (C. elegans) followed by whole-transcriptome RNA sequencing (RNA-seq), we provide the first neuronal circRNA data in C. elegans. We show that circRNAs are highly expressed in the neurons of C. elegans and are preferably derived from neuronal genes. More importantly, reverse complementary matches (RCMs) in circRNA-flanking introns are not only required for back-splicing but also promote the skipping of exon(s) to be circularized. Finally, through one-by-one mutagenesis of all the splicing sites and branch points required for exon-skipping and back-splicing, we show that exon-skipping is not absolutely required for back-splicing, neither the other way. Instead, the coupled exon-skipping and back-splicing are happening at the same time and the two pathways work together to regulate the levels of the circular and the skipped transcripts.

scholarly journals Reverse complementary matches simultaneously promote both back-splicing and exon-skipping

2021 ◽  
Author(s):  
Dong Cao
Keyword(s):  
Large Scale ◽  
Exon Skipping ◽  
Circular Rnas ◽  
Branch Points ◽  
C Elegans ◽  
Neuronal Genes ◽  
Almost All ◽  
First Time ◽  
The Brain

Abstract Background: Circular RNAs (circRNAs) play diverse roles in different biological and physiological environments and are always expressed in a tissue-specific manner. Especially, circRNAs are enriched in the brain tissues of almost all investigated species, including humans, mice, Drosophila, etc. Although circRNAs were found in C. elegans, the neuron-specific circRNA data is not available yet. Exon-skipping is found to be correlated to circRNA formation, but the mechanisms that link them together are not clear.Results: Here, through large-scale neuron isolation from the first larval (L1) stage of C. elegans followed by RNA sequencing with ribosomal RNA depletion, the first neuronal circRNA data in C. elegans were obtained. Hundreds of novel circRNAs were annotated with high accuracy. circRNAs were highly expressed in the neurons of C. elegans and were positively correlated to the levels of their cognate linear mRNAs. Disruption of RCMs in circRNA flanking introns effectively abolished circRNA formation. In the zip-2 gene, deletion of either upstream or downstream RCMs almost eliminated the production of both the circular and the skipped transcript. Interestingly, the 13-nt RCM in zip-2 is highly conserved across five nematode ortholog genes, which show conserved exon-skipping patterns. Finally, through in vivo one-by-one mutagenesis of all the splicing sites and branch points required for exon-skipping and back-splicing in the zip-2 gene, I showed that back-splicing still happened without exon-skipping, and vice versa.Conclusions: For the first time, total RNA obtained from sorted neurons is increased to hundreds of nanograms. circRNAs highly expressed in the neurons of C. elegans are likely derived from neuronal genes. RCMs are abundant in circRNA flanking introns, and RCM-deletion is an efficient way to knockout circRNAs. More importantly, these RCMs are not only required for back-splicing but also promote the skipping of exon(s) to be circularized. Finally, RCMs in circRNA flanking introns can directly promote both exon-skipping and back-splicing, providing a new explanation for the correlation between them.

scholarly journals Reverse complementary matches simultaneously promote both back-splicing and exon-skipping

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Dong Cao
Keyword(s):  
Ribosomal Rna ◽  
Large Scale ◽  
Exon Skipping ◽  
Circular Rnas ◽  
Branch Points ◽  
C Elegans ◽  
Almost All ◽  
The Brain ◽  
Rna Depletion

Abstract Background Circular RNAs (circRNAs) play diverse roles in different biological and physiological environments and are always expressed in a tissue-specific manner. Especially, circRNAs are enriched in the brain tissues of almost all investigated species, including humans, mice, Drosophila, etc. Although circRNAs were found in C. elegans, the neuron-specific circRNA data is not available yet. Exon-skipping is found to be correlated to circRNA formation, but the mechanisms that link them together are not clear. Results Here, through large-scale neuron isolation from the first larval (L1) stage of C. elegans followed by RNA sequencing with ribosomal RNA depletion, the neuronal circRNA data in C. elegans were obtained. Hundreds of novel circRNAs were annotated with high accuracy. circRNAs were highly expressed in the neurons of C. elegans and were positively correlated to the levels of their cognate linear mRNAs. Disruption of reverse complementary match (RCM) sequences in circRNA flanking introns effectively abolished circRNA formation. In the zip-2 gene, deletion of either upstream or downstream RCMs almost eliminated the production of both the circular and the skipped transcript. Interestingly, the 13-nt RCM in zip-2 is highly conserved across five nematode ortholog genes, which show conserved exon-skipping patterns. Finally, through in vivo one-by-one mutagenesis of all the splicing sites and branch points required for exon-skipping and back-splicing in the zip-2 gene, I showed that back-splicing still happened without exon-skipping, and vice versa. Conclusions Through protocol optimization, total RNA obtained from sorted neurons is increased to hundreds of nanograms. circRNAs highly expressed in the neurons of C. elegans are more likely to be derived from genes also highly expressed in the neurons. RCMs are abundant in circRNA flanking introns, and RCM-deletion is an efficient way to knockout circRNAs. More importantly, these RCMs are not only required for back-splicing but also promote the skipping of exon(s) to be circularized. Finally, RCMs in circRNA flanking introns can directly promote both exon-skipping and back-splicing, providing a new explanation for the correlation between them.

scholarly journals Global accumulation of circRNAs during aging in Caenorhabditis elegans

2017 ◽  
Author(s):  
Mariela Cortés-López ◽  
Matthew Gruner ◽  
Daphne A. Cooper ◽  
Hannah N. Gruner ◽  
Alexandru-Ioan Voda ◽  
...  
Keyword(s):  
Global Scale ◽  
Circular Rnas ◽  
Rna Seq ◽  
Aging Research ◽  
C Elegans ◽  
Fourth Larval Stage ◽  
Functional Consequences ◽  
Exceptional Stability ◽  
Massive Accumulation

SummaryCircular RNAs (CircRNAs) are a newly appreciated class of RNAs that lack free 5´ and 3´ ends, are expressed by the thousands in diverse forms of life, and are mostly of enigmatic function. Ostensibly due to their resistance to exonucleases, circRNAs are known to be exceptionally stable. Here, we examined the global profile of circRNAs in C. elegans during aging by performing ribo-depleted total RNA-seq from the fourth larval stage (L4) through 10-day old adults. Using stringent bioinformatic criteria and experimental validation, we annotated 1,166 circRNAs, including 575 newly discovered circRNAs. These circRNAs were derived from 797 genes with diverse functions, including genes involved in the determination of lifespan. A massive accumulation of circRNAs during aging was uncovered. Many hundreds of circRNAs were significantly increased among the aging time-points and increases of select circRNAs by over 40-fold during aging were quantified by qRT-PCR. The age-accumulation of circRNAs was not accompanied by increased expression of linear RNAs from the same host genes. We attribute the global scale of circRNA age-accumulation to the high composition of postmitotic cells in adult C. elegans, coupled with the high resistance of circRNAs to decay. These findings suggest that the exceptional stability of circRNAs might explain age-accumulation trends observed from neural tissues of other organisms, which also have a high composition of post-mitotic cells. Given the suitability of C. elegans for aging research, it is now poised as an excellent model system to determine if there are functional consequences of circRNA accumulation during aging.

scholarly journals Evaluation of deep-learning-based lncRNA identification tools

2019 ◽  
Author(s):  
Cheng Yang ◽  
Man Zhou ◽  
Haoling Xie ◽  
Huaiqiu Zhu
Keyword(s):  
Deep Learning ◽  
Large Scale ◽  
Full Length ◽  
The Other ◽  
Rna Seq ◽  
Partial Length ◽  
Overall Performance ◽  
Precision Recall Curve ◽  
Non Coding Rnas ◽  
Default Setting

Long non-coding RNAs (lncRNAs, length above 200 nt) exert crucial biological roles and have been implicated in cancers1,2. To characterize newly discovered transcripts, one major issue is to distinguish lncRNAs from mRNAs. Since experimental methods are time-consuming and costly, computational methods are preferred for large-scale lncRNA identification. In a recent study, Amin et al.3 evaluated three deep-learning-based lncRNA identification tools (i.e., lncRNAnet4, LncADeep5, and lncFinder6) and concluded “The LncADeep PR (precision recall) curve is just above the no-skill model and LncADeep showed poor overall performance”. This surprising conclusion is based on the authors’ use of a non-default setting of LncADeep. Actually, LncADeep has two models, one for full-length transcripts, and the other for transcripts including partial-length. Being aware of the difficulty of assembling full-length transcripts from RNA-seq dataset, LncADeep’s default model is for transcripts including partial-length. However, according to the results posted on Amin et al.’s website, the authors used LncADeep with full-length model, while they claimed to use the default setting of LncADeep, to identify lncRNAs from GENCODE dataset, which is composed of full- and partial-length transcripts. Thus, in their evaluation, the performance of LncADeep was underestimated. In this correspondence, we have tested LncADeep’s default setting (i.e., model for transcripts including partial-length) on the datasets used in Amin et al.3, and LncADeep achieved overall the best performance compared with the other tools’ results reported by Amin et al.

scholarly journals Whole-Transcriptome RNA Sequencing Reveals the Global Molecular Responses and CeRNA Regulatory Network of mRNAs, lncRNAs, miRNAs and circRNAs in Response to Salt Stress in Sugar Beet (Beta vulgaris)

2020 ◽  
Vol 22 (1) ◽  
pp. 289
Author(s):  
Junliang Li ◽  
Jie Cui ◽  
Cuihong Dai ◽  
Tianjiao Liu ◽  
Dayou Cheng ◽  
...  
Keyword(s):  
Salt Stress ◽  
Sugar Beet ◽  
Circular Rnas ◽  
Rna Seq ◽  
Plasma Membrane Permeability ◽  
Cerna Network ◽  
Mechanistic Basis ◽  
Whole Transcriptome ◽  
First Time ◽  
Competitive Endogenous Rna

Sugar beet is an important sugar-yielding crop with some tolerance to salt, but the mechanistic basis of this tolerance is not known. In the present study, we have used whole-transcriptome RNA-seq and degradome sequencing in response to salt stress to uncover differentially expressed (DE) mRNAs, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in both leaves and roots. A competitive endogenous RNA (ceRNA) network was constructed with the predicted DE pairs, which revealed regulatory roles under salt stress. A functional analysis suggests that ceRNAs are implicated in copper redistribution, plasma membrane permeability, glycometabolism and energy metabolism, NAC transcription factor and the phosphoinositol signaling system. Overall, we conducted for the first time a full transcriptomic analysis of sugar beet under salt stress that involves a potential ceRNA network, thus providing a basis to study the potential functions of lncRNAs/circRNAs.

scholarly journals Exploring Additional Valuable Information From Single-Cell RNA-Seq Data

2020 ◽  
Vol 8 ◽  
Author(s):  
Yunjin Li ◽  
Qiyue Xu ◽  
Duojiao Wu ◽  
Geng Chen
Keyword(s):  
Single Cell ◽  
Cell Biology ◽  
Large Scale ◽  
Cell Communication ◽  
Cell Types ◽  
Copy Number Variations ◽  
Developmental Trajectory ◽  
Cellular Heterogeneity ◽  
Circular Rnas ◽  
Rna Seq

Single-cell RNA-seq (scRNA-seq) technologies are broadly applied to dissect the cellular heterogeneity and expression dynamics, providing unprecedented insights into single-cell biology. Most of the scRNA-seq studies mainly focused on the dissection of cell types/states, developmental trajectory, gene regulatory network, and alternative splicing. However, besides these routine analyses, many other valuable scRNA-seq investigations can be conducted. Here, we first review cell-to-cell communication exploration, RNA velocity inference, identification of large-scale copy number variations and single nucleotide changes, and chromatin accessibility prediction based on single-cell transcriptomics data. Next, we discuss the identification of novel genes/transcripts through transcriptome reconstruction approaches, as well as the profiling of long non-coding RNAs and circular RNAs. Additionally, we survey the integration of single-cell and bulk RNA-seq datasets for deconvoluting the cell composition of large-scale bulk samples and linking single-cell signatures to patient outcomes. These additional analyses could largely facilitate corresponding basic science and clinical applications.

Birlikte Yaşama Kültürü Çerçevesinde Avrupa Birliği ve Türkiye Politikaları: Suriyelilere Yönelik Tutumun Sultanbeyli Örneği Üzerinden Değerlendirilmesi

2017 ◽  
Vol 4 (1) ◽  
pp. 41-61
Author(s):  
Pelin Sönmez ◽  
Abulfaz Süleymanov
Keyword(s):  
Civil Wars ◽  
Large Scale ◽  
Social Acceptance ◽  
Point Of View ◽  
The Other ◽  
Syrian Refugees ◽  
The European Union ◽  
International Protection ◽  
Legal Structure ◽  
Turkish People

Türkiye, Cumhuriyet tarihinin en yoğun zorunlu göç dalgasını 2011 yılından bu yana süren Suriye Savaşı ile yaşamaktadır. Suriye vatandaşlarının geçici koruma statüsü altında Türkiye toplumuna her açıdan entegrasyonları günümüzün ve geleceğin politika öncelikleri arasında düşünülmelidir. Öte yandan ülkeye kabul edilen sığınmacıların kendi kültürel kimliğini kaybetmeden içinde yaşadığı ev sahibi topluma uyumu, ortak yaşam kültürünün gelişmesi açısından önem arz etmektedir. Bu makalede, "misafir" olarak kabul edilen Suriyeli vatandaşların Türk toplumunca kabul edilmeleri ve dışlanma risklerinin azaltılmasına yönelik devlet politikaları ortaya konularak, üye ve aday ülkelere göçmenlerin dışlanmasını önlemek için Avrupa Birliği (AB) tarafından sunulan hukuki yapı ve kamu hizmeti inisiyatifleri incelenmekte, birlikte yaşam kültürü çerçevesinde Suriyeli vatandaşlara yönelik  toplumsal kabul düzeyleri ele alınmaktadır. Çalışma iki ana bölümden oluşmaktadır: göçmen ve sığınmacılara karşı toplumsal dışlanmayı engellemek için benimsenen yasa ve uygulamaların etkisi ve İstanbul-Sultanbeyli bölgesinde Suriyeli sığınmacılarla ilgili toplumsal algı çalışmasının sonuçları. Bölgede ikamet eden Suriyelilere yönelik toplumsal kabul düzeyinin yüksek olduğu görülürken, halkın Suriyelileri kendilerine  kültürel ve dini olarak yakın hissetmesi toplumsal kabul düzeyini olumlu etkilemektedir. ABSTRACT IN ENGLISHAn evaluation of the European Union and Turkish policies regarding the culture of living togetherThis article aims to determine the level of social acceptance towards Syrians within the context of cohabitation culture by evaluating EU’s legal structure and public service initiatives in order to prevent Syrian refugees from being excluded in member and candidate countries and by revealing government policies on acceptance of Syrians as “guest” by Turkish society and minimizing the exclusion risks of them. This article consists of two main parts, one of which is based on the effects of law and practices preventing refugees and asylum seekers from social exclusion, and the other is on the results of social perception on Syrians in Sultanbeyli district of Istanbul. At the end of 5-years taking in Syrian War, it is obvious that most of more than 3 million Syrian with unregistered ones in Turkey are “here to stay”. From this point of view, the primary scope of policies should be specified in order to remove side effects of refugee phenomenon seen as weighty matter by bottoming out the exclusion towards those people. To avoid possible large-scale conflicts or civil wars in the future, the struggle with exclusion phenomenon plays a crucial role regarding Turkey’s sociological situation and developing policies. In the meaning of forming a model for Turkey, a subtitle in this article is about public services for European-wide legal acquis and practices carried out since 1970s in order to prevent any exclusion from the society. On the other hand, other subtitles are about legal infrastructure and practices like Common European Asylum and Immigration Policies presented in 2005, and Law on Foreigners and International Protection introduced in 2013. In the last part of the article, the results of a field survey carried out in a district of Istanbul were used to analyze the exclusion towards refugees in Turkey. A face-to-face survey was randomly conducted with 200 settled refugees in Sultanbeyli district of Istanbul, and their perceptions towards Syrian people under temporary protection were evaluated. According to the results, the level of acceptance for Syrians living in this district seems relatively high. The fact that Turkish people living in the same district feel close to Syrian refugees culturally and religiously affect their perception in a positive way: however, it is strikingly seen and understood that local residents cop an attitude on the refugees’ becoming Turkish citizens.

HOME VISITS DURING THE FIRST MONTH OF DELIVERY FOR RECENTLY DELIVERED WOMEN IN UTTAR PRADESH, INDIA

2020 ◽  
Vol 6 (5) ◽  
pp. 1183-1189
Author(s):  
Dr. Tridibesh Tripathy ◽  
Dr. Umakant Prusty ◽  
Dr. Chintamani Nayak ◽  
Dr. Rakesh Dwivedi ◽  
Dr. Mohini Gautam
Keyword(s):  
Large Scale ◽  
National Level ◽  
Uttar Pradesh ◽  
Life Time ◽  
Structured Interview ◽  
The Other ◽  
Registration System ◽  
Action Group ◽  
Current Article ◽  
The Impact

The current article of Uttar Pradesh (UP) is about the ASHAs who are the daughters-in-law of a family that resides in the same community that they serve as the grassroots health worker since 2005 when the NRHM was introduced in the Empowered Action Group (EAG) states. UP is one such Empowered Action Group (EAG) state. The current study explores the actual responses of Recently Delivered Women (RDW) on their visits during the first month of their recent delivery. From the catchment area of each of the 250 ASHAs, two RDWs were selected who had a child in the age group of 3 to 6 months during the survey. The response profiles of the RDWs on the post- delivery first month visits are dwelled upon to evolve a picture representing the entire state of UP. The relevance of the study assumes significance as detailed data on the modalities of postnatal visits are available but not exclusively for the first month period of their recent delivery. The details of the post-delivery first month period related visits are not available even in large scale surveys like National Family Health Survey 4 done in 2015-16. The current study gives an insight in to these visits with a five-point approach i.e. type of personnel doing the visit, frequency of the visits, visits done in a particular week from among those four weeks separately for the three visits separately. The current study is basically regarding the summary of this Penta approach for the post- delivery one-month period.     The first month period after each delivery deals with 70% of the time of the postnatal period & the entire neonatal period. Therefore, it does impact the Maternal Mortality Rate & Ratio (MMR) & the Neonatal Mortality Rates (NMR) in India and especially in UP through the unsafe Maternal & Neonatal practices in the first month period after delivery. The current MM Rate of UP is 20.1 & MM Ratio is 216 whereas the MM ratio is 122 in India (SRS, 2019). The Sample Registration System (SRS) report also mentions that the Life Time Risk (LTR) of a woman in pregnancy is 0.7% which is the highest in the nation (SRS, 2019). This means it is very risky to give birth in UP in comparison to other regions in the country (SRS, 2019). This risk is at the peak in the first month period after each delivery. Similarly, the current NMR in India is 23 per 1000 livebirths (UNIGME,2018). As NMR data is not available separately for states, the national level data also hold good for the states and that’s how for the state of UP as well. These mortalities are the impact indicators and such indicators can be reduced through long drawn processes that includes effective and timely visits to RDWs especially in the first month period after delivery. This would help in making their post-natal & neonatal stage safe. This is the area of post-delivery first month visit profile detailing that the current article helps in popping out in relation to the recent delivery of the respondents.   A total of four districts of Uttar Pradesh were selected purposively for the study and the data collection was conducted in the villages of the respective districts with the help of a pre-tested structured interview schedule with both close-ended and open-ended questions.  The current article deals with five close ended questions with options, two for the type of personnel & frequency while the other three are for each of the three visits in the first month after the recent delivery of respondents. In addition, in-depth interviews were also conducted amongst the RDWs and a total 500 respondents had participated in the study.   Among the districts related to this article, the results showed that ASHA was the type of personnel who did the majority of visits in all the four districts. On the other hand, 25-40% of RDWs in all the 4 districts replied that they did not receive any visit within the first month of their recent delivery. Regarding frequency, most of the RDWs in all the 4 districts received 1-2 times visits by ASHAs.   Regarding the first visit, it was found that the ASHAs of Barabanki and Gonda visited less percentage of RDWs in the first week after delivery. Similarly, the second visit revealed that about 1.2% RDWs in Banda district could not recall about the visit. Further on the second visit, the RDWs responded that most of them in 3 districts except Gonda district did receive the second postnatal visit in 7-15 days after their recent delivery. Less than half of RDWs in Barabanki district & just more than half of RDWs in Gonda district received the third visit in 15-21 days period after delivery. For the same period, the majority of RDWs in the rest two districts responded that they had been entertained through a home visit.

Should all Hypertensive Patients be Screened for Primary Aldosteronism?

2019 ◽  
Vol 15 (1) ◽  
pp. 54-56
Author(s):  
Stelina Alkagiet ◽  
Konstantinos Tziomalos
Keyword(s):  
Resistant Hypertension ◽  
Primary Aldosteronism ◽  
Large Scale ◽  
Controlled Trial ◽  
The Other ◽  
Limited Data ◽  
Hypertensive Patients ◽  
Randomized Controlled ◽  
Increased Risk ◽  
Prospective Randomized Controlled Trial

Primary aldosteronism (PA) is not only a leading cause of secondary and resistant hypertension, but is also quite frequent in unselected hypertensive patients. Moreover, PA is associated with increased cardiovascular risk, which is disproportionate to BP levels. In addition, timely diagnosis of PA and prompt initiation of treatment attenuate this increased risk. On the other hand, there are limited data regarding the usefulness of screening for PA in all asymptomatic or normokalemic hypertensive patients. More importantly, until now, no well-organized, large-scale, prospective, randomized controlled trial has proved the effectiveness of screening for PA for improving clinical outcome. Accordingly, until more relevant data are available, screening for PA should be considered in hypertensive patients with spontaneous or diuretic-induced hypokalemia as well as in those with resistant hypertension. However, screening for PA in all hypertensive patients cannot be currently recommended.

Talking about MOTION in Middle English

2017 ◽  
Author(s):  
Judith Huber
Keyword(s):  
Middle English ◽  
Old English ◽  
Language Contact ◽  
Large Scale ◽  
The Other ◽  
Motion Verbs ◽  
Text Type ◽  
Anglo Norman ◽  
Contact Situation ◽  
Analysis Of Motion

Chapter 6 begins with an overview of the language contact situation with (Anglo-) French and Latin, resulting in large-scale borrowing in the Middle English period. The analysis of 465 Middle English verbs used to express intransitive motion shows that there are far more French/Latin loans in the path verbs than in the other motion verbs. The range of (new) manner of motion verbs testifies to the manner salience of Middle English: caused motion verbs are also found in intransitive motion meanings, as are French loans which do not have motion uses in continental French. Their motion uses in Anglo-Norman are discussed in terms of contact influence of Middle English. The analysis of motion expression in different texts yields a picture similar to the situation in Old English, with path typically expressed in satellites, and neutral as well as manner of motion verbs being most frequent, depending on text type.

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